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Research On The Season Influenza Vaccine For Epidemic Strains Of China

Posted on:2015-02-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:W YuFull Text:PDF
GTID:1224330488967649Subject:Pathogen Biology
Abstract/Summary:PDF Full Text Request
Influenza is a seasonal disease associated with significant morbidity and mortality. Vaccination is the most effective prophylactic method for preventing. At present, chicken embryo is used as substrate to produce influenza vaccine. Producted influenza virues in chicken embryo has many disadvantages such as the introduction of ovalbumin allergies which can cause human body allergy. It is difficult to supply a lot of chicken embryo for the production of vaccine in a short time. Meanwhile, chickens are highly susceptible to influenza virus, the supply of chicken embryos for vaccine production might be depleted during a influenza virus outbreak. Also it has been reported that virus are selected variation when influenza virus is passage in the embryo.Vero cells are recommended as a good substrate by WHO for cell cultures are easier to handle and can be scaled up in a short period of time. Virus propagated in mammalian-derived tissue culture have been reported to be antigenically more representative of the wild-type virus, and were shown to elicit higher levels of cross-reactive antibodies compared with egg-derived vaccines.It can induce superior protection against virus. Cell-based vaccines is the future developm-ent trend of the influenza vaccine.But,cell-based influenza production technology is very difficult for vero cells are not sensitivity to influenza viruses.Vero-adapted influenza virus is in low growth yield makes Vero cell-based influenza vaccine high cost and difficult to use in the market.Thus, how to fast educate influenza virus for high yield strain become a big problem. The World Health Organization (WHO) determined the composition of the new influenza vaccine each year spring for influenza virus continuous variation. It cannot accurate response China epidemic influenza virus variation and the vaccine’s protective power is reduced. As a big country,with population of 1.3 billion, to establish local epidemic influenza cell-based vaccine platform is particularly important. We got China epidemic influenza virus A/Tianjin/15/2009(H1N1), A/FujianTonang/196/2 009(H3N2), B/ChongqinYuzhong /1384/2010 (in chicken embryo yield is low, in Vero cell can’t copy)from the National Influenza Center, and replaced the PB2, PB1, PA, NP, M and NS genes with those of the A/Yunnan/1/2005Va(H3N2), A/SolomonIslands /3/2006Va (H1N1), B/Yamagata/16/88Va(B) which could be amplified with high titer in Vero cells by genetic reassortment technology. The reassortant influenza virus showed high hemagglutinin titer and stable replication ability in Vero cells. Once the influenza outbreaks, we can use this way to get high-yield Vero-adapted China epidemic influenza virus quickly to produce vaccine.Hemagglutinin protein, the most important target protein on the surface of the influ-enza virus for vaccination,can induce a protective immune response and reflect efficacy of influenza vaccine. In influenza vaccine production process, anther key step is vaccine standard antigen.WHO develop hemagglutinin protein standard antigen of new influenza virus two or three months later for vaccine production enterprises. Modeling of pandemic spread has shown that induction of an immune response to pandemic strain in a significa-nt proportion of the population within two weeks after the beginning of an outbreak is cr-ritical to interrupt virus transmission, further emphasizing the importance of timely and effective vaccination production.Due to china epidemic influenza virus is not WHO reco-mmended standard influenza strain, so how to fast produce hemagglutinin protein standa-d antigen is another problem of local epidemic influenza cell-based vaccine platform. W-HO has encouraged countries to prepare in advance by developing influenza preparedness plans that involve public health and pharmaceutical interventions.How to quantitative the HA content when standard antigen did not supply in time. In this study, we compared the purification effect in different pH conditions through ultracentrifugation. Based on this purification process, we added the bromelain and hemagglutinin protein were obtained. The process can be used for vaccine production enterprise to independent-ly develop hemagglutinin protein standard antigen.
Keywords/Search Tags:Vaccine, Influenza virus, Classic genetic reassortment technology, Purification, Hemagglutinin
PDF Full Text Request
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